We describe an optical tissue phantom that enables the simulation of drug extravasation from microvessels and validates
computational compartmental models of drug delivery. The phantom consists of a microdialysis tubing bundle to
simulate the permeable blood vessels, immersed in either an aqueous suspension of titanium dioxide (TiO2) or a TiO2
mixed agarose scattering medium. Drug administration is represented by a dye circulated through this porous
microdialysis tubing bundle. Optical pharmacokinetic (OP) methods are used to measure changes in the absorption
coefficient of the scattering medium due to the arrival and diffusion of the dye. We have established particle sizedependent
concentration profiles over time of phantom drug delivery by intravenous (IV) and intra-arterial (IA) routes.
Additionally, pharmacokinetic compartmental models are implemented in computer simulations for the conditions
studied within the phantom. The simulated concentration-time profiles agree well with measurements from the phantom.
The results are encouraging for future optical pharmacokinetic method development, both physical and computational, to
understand drug extravasation under various physiological conditions.
Multifocal recurrence of in-situ squamous cell cancer of the oral cavity, pharynx and vocal cord
following surgical failure can be a therapeutic dilemma. Salvage surgery or radiation may be an option but
morbidity can be significant. We evaluated the potential role of low dose Photofrin (1.2mg/Kg)
Photodynamic Therapy for this cohort of patients.
A total of 25 patients with multifocal recurrent in-situ squamous cell cancer of the oral cavity,
pharynx and vocal cord who had failed local resection, and where additional surgery or radiation therapy
would likely result in permanent morbidity, were offered Photodynamic Therapy. PDT consisted of off
label infusion of Photofrin (1.2mg/kg) followed 48 hours later by illumination at 630nm employing a light
diffuser (300J) and/or microlens (150Jcm2).
All patients completed their prescribed PDT and no patient has been lost to follow up (minimum 1
year). No photosensitivity reactions were noted. No significant morbidity was seen. All patients were able
to maintain oral nutrition. Procedure related pain was well controlled by one week of oral narcotics. At
one month post PDT all patients were biopsy negative in the treatment region and no failures within the
treatment region have been noted. No fibrosis or permanent PDT morbidity has been seen with follow up to
three years. Vocal cord and voice function were excellent.
Three patients developed new regions of in-situ disease outside the PDT fields, two underwent additional
PDT and one had laser resection.
Low dose Photofrin PDT offers excellent palliation and durable local control of recurrent in-situ
squamous cell cancers of the oral cavity, pharynx and true cords. This is a well tolerated therapy. Low
dose Photofrin appears to improve selectivity and minimize normal tissue injury. It should be tested in a
larger patient population.
The short and long term stability of the Diomed 630 PDT laser with attached fiberoptic microlens was evaluated by
means of integrating sphere, power meter and a calorimetric system. The calorimeter system was designed as a thermal
mug with absorbing media (dye and water). Both the tip of the irradiation fiber and the detection probe of a
thermocouple thermometer were positioned inside the dye solution and stirred during the measurements. The
calorimetric system yielded measurement results consistent with the other two methods, and similar long term variations
were observed by all methods. With an indicated laser power of 1 W, the detectors' readings ranged from 0.66 to 1.29
W. For short term stability study, the deviation of laser output assessed by integrating sphere, power meter and
calorimetric system were 0.3%, 0.1% and 2.8% with long term deviations of 13%, 7% and 9% respectively. This wide
variation in the laser output implies the needs to establish quality control procedures involving measurements pre and
post PDT procedures. The calorimetric system has been demonstrated to be a powerful tool for clinical laser QA and
maintenance of the calibration factor of the detectors used in this work.
Fluorescence measurements have been used to track the dosimetry of photodynamic therapy (PDT) for many years, and this approach can be especially important for treatments with aminolevulinic-acid-induced protoporphyrin IX (ALA-PpIX). PpIX photobleaches rapidly, and the bleaching is known to be oxygen dependent, and at the same time, fractionation or reduced irradiance treatments have been shown to significantly increase efficacy. Thus, in vivo measurement of either the bleaching rate and/or the total bleaching yield could be used to track the deposited dose in tissue and determine the optimal treatment plans. Fluorescence in rat esophagus and human Barrett's esophagus are measured during PDT in both continuous and fractionated light delivery treatment, and the bleaching is quantified. Reducing the optical irradiance from 50 to 25 mW/cm did not significantly alter photobleaching in rat esophagus, but fractionation of the light at 1-min on and off intervals did increase photobleaching up to 10% more (p value=0.02) and up to 25% more in the human Barrett's tissue (p value<0.001). While two different tissues and two different dosimetry systems are used, the data support the overall hypothesis that light fractionation in ALA-PpIX PDT esophageal treatments should have a beneficial effect on the total treatment effect.
In order to better understand light dosimetry issues for photodynamic therapy (PDT), we have used various tumor and normal tissue geometries to develop a diffusion model of light transport in tissues. We hypothesize that tumor tissues with curved surfaces will have significantly different internal fluence distributions, as compared to tissues with flat surfaces. Using a mouse subcutaneous tumor and rear limb muscle model we compared the internal fluence values within the tissue. In addition, numerical simulations for these corresponding tissue geometries and laser light incidence angles were made. Assuming that the relative photon fluence in the tissue can be accurately modeled by the diffusion equation, we used a finite element approach to approximate the distribution inside the tissue. Meshes with different geometries (flat and curved with different curvatures) were used in this study to mimic the tumor and leg geometries of the murine tumors treated in the lab. Results suggest that tissues surface geometries and incidence angle of light can significantly alter the photon fluence inside the tissue. The photon fluence difference for an 8 mm diameter, curved surface mouse tumor vs. flat muscle tissue can be as high as 20%. In general, the greater the tissues curvature, the greater the potential loss in light fluence is. In summary, our data demonstrates the importance of tissue surface geometry and the incidence angle of light in determining optimal PDT light dosimetry, and indicates that comparisons between tissue geometries must be carried out with attention to differences in the internal optical distribution.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.